The redox sensor TXNL1 plays a regulatory role in fluid phase endocytosis.

The redox sensor TXNL1 plays a regulatory role in fluid phase endocytosis.
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氧化还原传感器TXNL1在液相内吞作用中起调节作用。

DOI:
10.1371/journal.pone.0001144
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发表时间:
2007-11-07
期刊:
影响因子:
3.7
通讯作者:
Gruenberg, Jean
Gruenberg, Jean
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Felberbaum-Corti, Michela;Morel, Etienne;Cavalli, Valeria;Vilbois, Francis;Gruenberg, Jean

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Rab家族的小GTP酶可以在GTP和GDP结合的状态之间循环,也可以在膜和胞浆之间循环。后者是由鸟嘌呤核苷酸解离抑制剂GDI介导的,它可以选择性地从供体膜上提取与GDP结合的Rab蛋白,然后将它们重新装载到靶膜上。在以前的研究中,我们发现GDI通过p38MAPK在氧化应激的刺激下捕获小GTP酶Rab5,导致液相内吞作用增加。在纯化GDI刺激活性时,我们发现它与包括p38MAPK在内的高相对分子质量的蛋白复合体结合。在这里,我们报告了该复合体的另一组分的鉴定和特性,即硫氧还蛋白样蛋白TXNL1。我们的观察表明,TXNL1通过控制GDI捕获Rab5的能力,在液体相内吞作用中发挥选择性作用。已知会导致细胞损伤的氧化剂也可以触发信号通路,特别是通过硫氧还蛋白家族的成员。我们认为TXNL1作为氧化剂的效应器或氧化还原传感器,通过将氧化还原的变化转化为GDI容量的变化来捕获Rab5,进而调节液体相的内吞作用。
Small GTPases of the Rab family can cycle between a GTP- and a GDP-bound state and also between membrane and cytosol. The latter cycle is mediated by the Guanine Nucleotide Dissociation Inhibitor GDI, which can selectively extract GDP-bound Rab proteins from donor membranes, and then reload them on target membranes. In previous studies, we found that capture of the small GTPase Rab5, a key regulator of endocytic membrane traffic, by GDI is stimulated by oxidative stress via p38MAPK, resulting in increased fluid phase endocytosis. When purifying the GDI stimulating activity we found that that it copurified with a high MW protein complex, which included p38MAPK. Here we report the identification and characterization of another component of this complex as the thioredoxin-like protein TXNL1. Our observations indicate that TXNL1 play a selective role in the regulation of fluid phase endocytosis, by controlling GDI capacity to capture Rab5. Oxidants, which are known to cause cellular damage, can also trigger signaling pathways, in particular via members of the thioredoxin family. We propose that TXNL1 acts as an effector of oxidants or a redox sensor by converting redox changes into changes of GDI capacity to capture Rab5, which in turn modulates fluid phase endocytosis.
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